Aim To compare the immunogenicity and frequency of persistent infection and cervical precancerous lesions caused by vaccine-targeted HPV after vaccination with: Two doses of quadrivalent vaccine on days 1 and 180 or later With three doses on days 1, 60, and 180 or later, in a cluster-randomised trial

1. Two – Dose regime of 4HPV :
Indian Perspective
Dr. Jyoti Agarwal
Dr. Sharda Jain
…..Caring hearts, healing hands

2. Published online December 1, 2015 www.thelancet.com/oncology
Evidence supporting 2-Dose study
of 4HPV
Sankaranarayanan et al, Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in
girls in India: a multicentre prospective cohort study Published online December 1, 2015 www.thelancet.com/oncology
An Independent Study done by International Agency for Research on Cancer
Funded by Bill & Melinda Gates Foundation

3. Aim
• To compare the immunogenicity and frequency
of persistent infection and cervical precancerous
lesions caused by vaccine-targeted HPV after
vaccination with:
• Two doses of quadrivalent vaccine on
days 1 and 180 or later
• With three doses on days 1, 60, and 180
or later, in a cluster-randomised trial

4. Hyderabad, Osmanabad,
Dindigul
Pune, Mumbai
Ahmedabad
Delhi
Gangtok
Aizwal
Salient features of the study
• Large,multicentre,
prospective study
• Indian data
• Study was done in 9
locations in India
(188 clusters)

5. Study design and Participants
• Participants were unmarried girls aged 10–18 years
vaccinated in four cohorts:
• Girls who received three doses of vaccine on
days 1, 60, and 180 or later
• Two doses on days 1 and 180 or later
• Two doses on days 1 and 60 by default
• One dose by default
• Done from Sept 1, 2009 - Apr 2010 and
• Median follow up was 4.7yr
• No serious adverse events were noted with vaccine

6. Primary outcomes
• Immunogenicity outcomes
– HPV-L1 genotype-specific binding Ab
concentrations, Antibody avidity
– Ab concentrations specific for
neutralising epitopes in HPV-L1 using
GMTs
• Infection outcomes
– first incident and persistent infections
of vaccine targeted HPV types during
follow-up.

7. Assessments done
• Ab titres: Blood samples obtained by nurses during
the vaccination session at a clinic or during
household visits on day 1 and
7 – 12 –18 – 24 – 36 – 48 – 60 months
• Cervical samples: Pelvic examination done at 18
months after marriage or 6 months after delivery of
their first child, whichever was earlier and every year
thereafter for 3 years.

8. Results:Subject recruitment
17729 girls
(10-18yr)
1D default (n=4950) (28%)
Day1
2D default (n=3452) (19%)
Days 1 & 60
2D (n=4979) (28%)
Days1,180
3 D (n=4348) (25%)
Days 1,60,180

9. Results:Mean MFI (median fluorescence intensity)
HPV types 16, 18, 6, and 11 L1 antibodies
Dashed lines show the threshold (cutoff ) values for seroconversion. MFI=median fluorescence intensity. *MFI values for month 7 were used for
the three-dose and two-dose vaccine groups, whereas MFI values for month 12 were used for the two-dose default and one-dose default groups.

10. Results: Persistent infection
In 838 women for whom two or more
samples were available for analysis,
there were NO persistent HPV 16 and
18 infections in any of the four study
groups at a median follow-up of 4·7
years
2649 participants contributed cervical samples
838 had 2 or more samples

11. Summary
• Two doses of quadrivalent HPV vaccine (10-18yr),
administered at an interval of 180 days or more
immunologically non-inferior to the three-
dose schedule and
afford protection against incident and
persistent HPV 16, 18, 6, and 11 infections
similar to that afforded by three doses
Findings support the WHO recommendation
to use two doses separated by 6 months for
vaccination of young girls

12. WHO (Strategic Advisory Group of Experts )
SAGE recommends that the immunological evidence is
sufficient to conclude that a
• 2-dose prime-boost schedule (given with a minimal
interval of 6 months)
was non-inferior to a
• 3-dose (prime-prime-boost, at 0, 1–2, and 6 months)
schedule
For Adolescent Girls Aged 9-14 Years
Weekly epidemiological record, 23 MAY 2014, 89th year, No. 21, 2014, 89, 221–236

13. IAP Recommendations
• Only 2 doses of either of the 2 HPV vaccines for adolescent/pre-adolescent girls
aged 9-14 years.
• For girls 15 years and older and immunocompromised individuals 3 doses are
recommended
• For 2 –dose schedule, the minimum interval between doses should be 6
months
• For 3 dose schedule, the doses can be administered at 0, 1-2 (depending on
brands) and 6 months.
VASHISHTHA et al, Indian Academy of Pediatrics (IAP) Recommended Immunization Schedule for Children Aged 0 through 18 years – India,
2014 and Updates on Immunization VOLUME 51__OCTOBER 15, 2014

14. Countries Currently Implementing Alternate Dosing Schedules
Canada
Quebec &
BC
Mexico Switzerland Colombia South Africa Brazil Austria
Schedule
Quebec
0-6 months
0-6-60 months 0-4 or 0-6
months
0-6 months 0-6 months 0-6-60 months 0-6 months
BC
0-6-36 months
Starting
age
Quebec
9 y.o girls
(4th grade)
9 years old 11-14 y.o. girls
(First dose
before 15th
birthday)
9-18 y.o. girls
(4th grade –
12th grade)
9 -10 y.o. girls 11-13 y.o. girls in
2014
9-11 y.o. girls in
2015
9 y.o boys &
girls
BC
11 to 12 y.o.
girls
(6th grade)
3rd dose
Quebec: No 3rd
D
BC: 14 to 15
y.o.
(9th grade)
Third dose if
proven
necessary
Third dose
being
considered
(at month 60)
Third dose if
proven
necessary
Third dose being
considered
(at month 60)
Brand
Choice
2013/201
4
100% Gardasil
Since Launch
2013 MOH:
100% Cervarix
Previously
GRD
90% Gardasil
Since Launch
100%
Gardasil
Since Launch
100% Cervarix 100% Gardasil
Most probably
Gardasil
1
4

15. 2-Dose: Global Regulatory Status (73)
7 NORTH AMERICA
Canada Jamaica
Mexico El Salvador
Costa Rica Honduras
Dominican Republic
ASIA PACIFIC
Hong Kong Thailand
Korea Philippines
Taiwan Sri Lanka
Malaysia Pakistan
Singapore Indonesia
Kazakhstan
SOUTH AMERICA
Brazil Venezuela
Colombia
Argentina
Peru
Ecuador
Trinidad & Tobago
MIDDLE EAST &
AFRICA
Brunei Turkey
Israel
South Africa
EUROPE
Austria
Belgium
Bulgaria
Croatia
Cyprus
Czech Republic
Denmark
Estonia
Finland
France
Serbia
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Lithuania
Luxembourg
Malta
Macedonia
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Bosnia &
Herzegovina
33
7
11
CIS Countries
Armenia Georgia
Aruba Moldova
Azerbaijan Ukraine
Turkmenistan Uzbekistan
Belarus Russian Federation
10
4

16. Dobson SRM et al.JAMA 2013;309 (17):1793-1802
Results consistent with data from
other countries

17. CONCLUSION
Based on the
 Clinical Trial data
 WHO Recommendation
 IAP Recommendation and
 Approval in key countries
HPV vaccination is now approved to be used in a
2-dose alternative schedule, at 0 and 6 months,
for girls 9 to 14 years old, in India

18. Thank
you